Testosterone recovery following androgen suppression and prostate radiotherapy (TRANSPORT): Updated individual patient data meta-analyses from the MARCAP consortium.
Authors: Wee Loon Ong, Holly Wilhalme, Jeremy Laurence Millar, Allison Steigler, James William Denham, David John Joseph, Soumyajit Roy, Shawn Malone, Nicholas George Nickols, Matthew Rettig, Luca Faustino Valle, Michael L. Steinberg, Yilun Sun, Nicholas George Zaorsky, Daniel Eidelberg Spratt, Luis Souhami, Nathalie Carrier, Abdenour Nabid, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2023)

5096 Background: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) and radiotherapy for prostate cancer varies following cessation of ADT. We aimed to quantify the association between time to TR and duration of ADT and patient age. Methods: We identified prospective randomized trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone values were available. The time to non-castrate TR (NCTR) (&gt;1.7ng/mL), non-hypogonadal TR (NHTR) (&gt;8.0ng/mL) and full TR (FTR) (&gt;10.5ng/mL) were estimated from the end date of prescribed ADT using the Kaplan Meier method. Cox regression was used to evaluate the differences in time to TR for men aged &lt;65 years and ≥65 years for each duration of ADT. Interaction effects between ADT duration and patient age on TR were evaluated. Results: 2628 men from 5 trials (TROG 9601, TROG 0304, PCSIII, PCSIV, and Ottawa-01) met the inclusion criteria for analysis. Of these, 236, 1485, 731, and 176 men had 3-, 6-, 18-, and 36-months of ADT respectively. 1502 (57%) men had baseline (pre-ADT) testosterone data available, of which 99% (1494/1502) had non-castrate testosterone (&gt;1.7ng/mL), and 78% (1178/1502) had normal testosterone (&gt;10.5ng/mL) at baseline. At last follow-up, there were 96% (2522/2628), 77% (2035/2628) and 65% (1700/2628) of men who had NCTR, NHTR and FTR respectively. The median time (range) to NCTR was 1.9 (0.2-60), 6.2 (0.0-92), 6.3 (0.0-92), and 15.7 (0.1-75) months for men who had 3-, 6-, 18- and 36-months of ADT, respectively. The median time (range) to NHTR was 2.5 (0.4-73), 11.2 (0.1-93), 17.7 (0.2-92), and 53.4 (5.3-76) months for men who had 3-, 6-, 18- and 36-months of ADT, respectively. The median time (range) to FTR was 5.8 (0.4-72), 16.7 (0.3-95), and 26.0 (0.2-90) for men who had 3-, 6-, and 18-months of ADT, respectively, while the median time to FTR was not reached in men who had 36-months of ADT. In men who had 6-months of ADT, men aged ≥65 years were 35% (95%CI=26-43%) less likely to have FTR compared to men aged &lt;65 years, while for those who had 18-months of ADT, men aged ≥ 65 years were 52% (95%CI=41-60%) less likely to have FTR compared to men aged &lt; 65 years. There was no statistically significant interaction between the effect of ADT duration and age on the time to FTR (interaction P=0.07 for the entire cohort). Conclusions: In this updated individual patient-data meta-analysis of prospectively collected serial testosterone data from 5 randomized trials, substantial delay in FTR in men who had longer duration of ADT was observed, consistent with prior analyses. Approximately 1-in-3 men did not have FTR, which may have life-long impacts on their quality of life.